The purpose of this project was to synthesize alpha-methyl-L-tryptophan (AMT) labeled with carbon-11 (T1/2 = 20.4 min), a cyclotron produced, positron-emitting radionuclide, which will permit imaging the brain utilizing positron emission tomography (PET). Drs. Paul Andreason and Susan Shoaf are interested in using PET to study the use of [11C]AMT as a tracer of brain serotonin synthesis. The rate of accumulation of radioactivity of this tracer as measured by PET is assumed to be indicative of the rate of serotonin synthesis and may be correlated with increased aggressive/impulsive behavior of patients. It was necessary to separate racemic AMT into its L- and D-isomers using a chiral HPLC column. The L-isomer was identified using an in vitro tryptophan hydrolyase enzyme assay. This permitted the determination of the pharmacokinetic parameters of AMT and the differences of the enzyme kinetics of AMT and tryptophan in order to relate the accumulation of AMT to the rate of serotonin synthesis. AMT has been synthesized in > 98% enantiomeric purity from a chiral pyrroloindole derivative which is commercially available. The procedure had to be significantly modified to synthesize [11C]AMT. This was accomplished yielding [11C]AMT with a radiopurity > 99% and a radiochemical yield of about 40%. No D-isomer could be detected by electrochemical HPLC analysis. [11C]AMT (1.5 to 5 mCi) was injected in three monkeys to determine the brain uptake and absorbed radiation dose. Whole body scans were obtained using the General Electric Advance. The average residence times for lung, liver, kidney, brain, and heart were: 0.67, 1.44, 1.52, 0.22, and 0.21 min, respectively. The kidney is the critical organ at 0.022 mGy/mBq (0.083 rad/mCi). Time- activity curves in monkey brain were determined for cortical gray matter, subcortical gray matter, and white matter.